HIV infection raised the risk of intracranial hemorrhage 5 times in a Quebec study comparing people with and without HIV [1]. Further analysis in the HIV group found no link between antiretroviral therapy or any antiretroviral class and risk of intracranial hemorrhage. None of the people taking tipranavir had an intracranial hemorrhage.

Intracranial hemorrhage may be caused by stroke or a ruptured aneurysm. Earlier research found a higher risk of intracranial hemorrhage in people with HIV and among people taking certain antiretrovirals, including the protease inhibitor tipranavir [2]. Rates of intracranial hemorrhage in earlier studies ranged from 7 per 10,000 person-years in a VA-California Medicaid study [3] to 26 per 10,000 in an analysis of the Adverse Events Reporting System [2].

To further explore intracranial hemorrhage in HIV-infected people, Montreal researchers selected all HIV-positive people enrolled in the RAMQ database between 1985 and 2007. The investigators matched this group to four HIV-negative controls according to gender, age, and follow-up period. To assess the impact of antiretrovirals on intracranial hemorrhage, the researchers also compared HIV-positive people with intracranial hemorrhage and up to 10 HIV-positive people without this diagnosis. Again, they matched cases and controls by gender, age, and follow-up dates.

The first comparison involved 7053 people with HIV and 27,681 people without HIV. Total follow-up time exceeded 138,000 person-years. There were 29 diagnoses of intracranial hemorrhage in the HIV group and 21 in the HIV-negative group. Intracranial hemorrhage rates were 8.01 per 10,000 person-years in the HIV group and 2.05 per 10,000 person-years in the non-HIV group. Statistical analysis that factored in other intracranial hemorrhage risk factors (age, gender, diabetes, hypertension, antiplatelet therapy, thrombosis, hemophilia, nonsteroidal antiinflammatories, and intracranial neoplasia) determined that HIV infection independently raised the risk of hemorrhage almost 5 times: hazard ratio 4.92, 95% confidence interval 2.76 to 8.79.

The second comparison involved the 29 HIV-positive people with intracranial hemorrhage and 228 matched HIV-positive controls without hemorrhage. Twenty-four people with intracranial hemorrhage had taken antiretrovirals. Neither exposure to antiretrovirals nor exposure to any antiretroviral class raised the risk of intracranial hemorrhage in this comparison. The investigators noted, though, that because they saw few cases of intracranial hemorrhage, this analysis had limited power to evaluate the impact of antiretroviral class. They also cautioned that they could not stratify the HIV-hemorrhage group by diagnosis of AIDS or opportunistic infection, CD4 count, or viral load.

"Even in the post HAART era," the investigators concluded, "HIV infection remains a significant risk factor for intracranial hemorrhage." However, rates in this study were much lower than reported in all but the VA study, probably because AIDS prevalence was higher in earlier studies.